Heterogeneity of the mesotelencephalic dopamine fibers: physiology and pharmacology

The mesotelencephalic dopamine (DA) system is heterogeneous with respect to nuclei, terminal loci, DA receptor subtypes, electro-physiological charact eristics and response patterns, and neuropharmacological response to a rang e of agents. The majority of mesocortical and mesolimbic DA neurons origina te in the ventral tegmental area. Mesostriatal DA neurons originate in subs tantia nigra pars compacta. DA neurons originating from the retrorubal fiel d primarily innervate subcortical limbic and neostriatal loci. Mesostriatal terminal loci have relatively low densities of D3 and D4 receptors, compar ed to mesolimbic and mesocortical loci. The D1 and D2 receptors appear more homogeneously distributed. Electrophysiologically, mesostriatal DA neurons show more regularity in firing pattern (fewer bursting events), and a lowe r basal firing rate than mesolimbic or mesocortical neurons. Neuropharmacol ogically, mesocortical DA neurons are less responsive to intravenous d-amph etamine, (+)apomorphine, and chronic antipsythotic drug treatment. Mesocort ical DA neurons are also relatively insensitive to iontophoretically applie d DA, a finding congruent with their reported relative lack of somatodendri tic autoreceptors. Neurochemically, mesoaccumbens DA neurons are more sensi tive to systemic administration of drags with addictive liability. (C) 2000 Elsevier Science Ltd. All rights reserved.